Lack of association between SOCS3 rs4969170 and interleukin 28B genes with therapeutic response in Brazilian HCV carriers treated with PEG-IFN/RBV

Abstract

Chronic HCV infections are related with the production of inappropriate cytokine levels in inflammatory and immune response. IFN-α must activate a signal transduction cascade that involves different intracellular proteins driving interferon-inducible genes to be activated. The proteins suppressor of cytokine signaling (SOCS) represents the main cellular mechanism for cytokine (such as IL10 and IFN) negative regulation. Immune responses may be associated with SOCS3 production driven by therapy against HCV and it seems to be regulated by single nucleotide polymorphisms (SNPs) within SOCS3 gene. Recently, genome-wide association studies have linked response to PEG-IFN/RBV therapy with SNPs near the IL28B gene (rs12979860), encoding for interferon-lambda-3 (IL28B). The rs12979860 CC genotype is associated with a greater rate of sustained virological response (SVR) than the CT or TT genotypes in different HCV patients populations. In this study, we evaluated the frequencies of SOCS3 and IL28B polymorphisms genes and their association with the response to IFN based antiviral therapy in chronic hepatitis C infection. After IRB ethics approval, frozen samples from 142 HCV Genotype-1 infected Brazilian patients were analyzed. Genomic DNA from patients classified as responders (R=71) and nonresponders (NR=71) to a PEG-IFN/RBV therapy were used in this study. The SNPs near the IL28B (rs12979860) and SOCS3 (rs4969170) genes were examined using an assay with allele specific PCR probes. According recent publications, IL28B CC genotype was considered the more favorable profile to reach Sustained Virologic Response (SVR). Regarding SOCS3 AA genotype was also recently strongly associated with failure of the IFN-α based therapy. The results are summarized in the table 1. As expected IL28B CC SNP was associated with a better response to antiviral therapy. Conversely, we could not observe a clear association between the polymorphism rs4969170 SOCS3 gene and lack of response to IFN based therapy in our population. Therefore we conclude that the SOCS3 rs4969170 was not as good as IL28B on predicting therapy outcome for HCV.